tbuckley/cabot-search huggingface dataset:
Proteomics separates adult-type diffuse high-grade gliomas in metabolic subgroups independent of 1p/19q codeletion and across IDH mutational status
Authors: Jakob Maximilian Bader, Nikolaus Deigendesch, Martin Misch, Matthias Mann, Arend Koch, Felix Meissner
Journal: Cell Reports Medicine (2022)

High-grade adult-type diffuse gliomas are malignant neuroepithelial tumors with poor survival rates in combined chemoradiotherapy. The current WHO classification is based on IDH1/2 mutational and 1p/19q codeletion status. Glioma proteome alterations remain undercharacterized despite their promise for a better molecular patient stratification and therapeutic target identification. Here, we use mass spectrometry to characterize 42 formalin-fixed, paraffin-embedded (FFPE) samples from IDH-wild-type (IDHwt) gliomas, IDH-mutant (IDHmut) gliomas with and without 1p/19q codeletion, and non-neoplastic controls. Based on more than 5,500 quantified proteins and 5,000 phosphosites, gliomas separate by IDH1/2 mutational status but not by 1p/19q status. Instead, IDHmut gliomas split into two proteomic subtypes with widespread perturbations, including aerobic/anaerobic energy metabolism. Validations with three independent glioma proteome datasets confirm these subgroups and link the IDHmut subtypes to the established proneural and classic/mesenchymal subtypes in IDHwt glioma. This demonstrates common phenotypic subtypes across the IDH status with potential therapeutic implications for patients with IDHmut gliomas.
Metabolic adaptation supports enhanced macrophage efferocytosis in limited-oxygen environments
Authors: Ya-Ting Wang, Alissa J. Trzeciak, Waleska Saitz Rojas, Pedro Saavedra, Yan-Ting Chen, Rachel Chirayil, Jon Iker Etchegaray, Christopher D. Lucas, Daniel J. Puleston, Kayvan R. Keshari, Justin S.A. Perry
Journal: Cell Metabolism (2022)
Brainstem serotonin neurons selectively gate retinal information flow to thalamus
Authors: Jasmine D.S. Reggiani, Qiufen Jiang, Melanie Barbini, Andrew Lutas, Liang Liang, Jesseba Fernando, Fei Deng, Jinxia Wan, Yulong Li, Chinfei Chen, Mark L. Andermann
Journal: Neuron (2022)
Determinants of resistance to engineered T cell therapies targeting CD19 in large B cell lymphomas
Authors: Brian J. Sworder, David M. Kurtz, Stefan K. Alig, Matthew J. Frank, Navika Shukla, Andrea Garofalo, Charles W. Macaulay, Mohammad Shahrokh Esfahani, Mari N. Olsen, James Hamilton, Hitomi Hosoya, Mark Hamilton, Jay Y. Spiegel, John H. Baird, Takeshi Sugio, Mia Carleton, Alexander F.M. Craig, Sheren F. Younes, Bita Sahaf, Natasha D. Sheybani, Joseph G. Schroers-Martin, Chih Long Liu, Jean S. Oak, Michael C. Jin, Sara Beygi, Andreas Hüttmann, Christine Hanoun, Ulrich Dührsen, Jason R. Westin, Michael S. Khodadoust, Yasodha Natkunam, Robbie G. Majzner, Crystal L. Mackall, Maximilian Diehn, David B. Miklos, Ash A. Alizadeh
Journal: Cancer Cell (2022)
Integrated multi-omics profiling yields a clinically relevant molecular classification for esophageal squamous cell carcinoma
Authors: Zhihua Liu, Yahui Zhao, Pengzhou Kong, Yuhao Liu, Jing Huang, Enwei Xu, Wenqing Wei, Guangyu Li, Xiaolong Cheng, Liyan Xue, Yi Li, Hongyan Chen, Shuqing Wei, Ruifang Sun, Heyang Cui, Yongsheng Meng, Meilin Liu, Yang Li, Riyue Feng, Xiao Yu, Rui Zhu, Yenan Wu, Lei Li, Bin Yang, Yanchun Ma, Jiawei Wang, Wenjie Zhu, Dongjie Deng, Yanfeng Xi, Fang Wang, Hongyi Li, Shiping Guo, Xiaofei Zhuang, Xiaoyue Wang, Yuchen Jiao, Yongping Cui, Qimin Zhan
Journal: Cancer Cell (2022)
Biomarkers of tumor-reactive CD4<sup>+</sup>and CD8<sup>+</sup>TILs associate with improved prognosis in endometrial cancer.
Authors: Jara Palomero, Carla Panisello, Maria Lozano-Rabella, Ricky Tirtakasuma, Judit Díaz-Gómez, Daniela Grases, Helena Pasamar, Laura Arregui, Eduard Dorca Duch, Esther Guerra Fernández, Ana Vivancos, Carlos E de Andrea, Ignacio Melero, Jordi Ponce, August Vidal, Josep Maria Piulats, Xavier Matias-Guiu, Alena Gros
Journal: Journal for ImmunoTherapy of Cancer (2022)

Despite the growing interest in immunotherapeutic interventions for endometrial cancer (EC), the prevalence, phenotype, specificity and prognostic value of tumor infiltrating lymphocytes (TILs) in this tumor type remains unclear.To better understand the role of TILs in EC, we analyzed the phenotypic traits of CD8+ and CD4+ EC-resident T cells from 47 primary tumors by high-dimensional flow cytometry. In addition, CD8+ and CD4+ TIL subpopulations were isolated based on the differential expression of programmed cell death protein-1 (PD-1) (negative, dim and high) and CD39 (positive or negative) by fluorescence activated cell sorting (FACS), expanded in vitro, and screened for autologous tumor recognition. We further investigated whether phenotypic markers preferentially expressed on CD8+ and CD4+ tumor-reactive TIL subsets were associated with the four distinct molecular subtypes of EC, tumor mutational burden and patient survival.We found that CD8+TILs expressing high levels of PD-1 (PD-1hi) co-expressed CD39, TIM-3, HLA-DR and CXCL13, as compared with TILs lacking or displaying intermediate levels of PD-1 expression (PD-1- and PD-1dim, respectively). Autologous tumor reactivity of sorted and in vitro expanded CD8+ TILs demonstrated that the CD8+PD-1dimCD39+ and PD-1hiCD39+ T cell subsets both contained tumor-reactive TILs and that a higher level of PD-1 expression was associated with increased CD39 and a superior frequency of tumor reactivity. With respect to CD4+ T conventional (Tconv) TILs, co-expression of inhibitory and activation markers was more apparent on PD-1hi compared with PD-1- or PD-1dim T cells, and in fact, it was the CD4+PD-1hi subpopulation that accumulated the antitumor T cells irrespective of CD39 expression. Most importantly, detection of CD8+PD-1hiCD39+ and CD4+PD-1hi tumor-reactive T-cell subsets, but also markers specifically expressed by these subpopulations of TILs, that is, PD-1hi, CD39, CXCL13 and CD103 by CD8+ TILs and PD-1hi and CXCL13 by CD4+ Tconv TILs, correlated with prolonged survival of patients with EC.Our results demonstrate that EC are frequently infiltrated by tumor-reactive TILs, and that expression of PD-1hi and CD39 or PD-1hi can be used to select and expand CD8+ and CD4+ tumor-reactive TILs, respectively. In addition, biomarkers preferentially expressed on tumor-reactive TILs, rather than the frequency of CD3+, CD8+ and CD4+ lymphocytes, hold prognostic value suggesting their protective role in antitumor immunity.
Alveolar ridge preservation: Complications and <scp>cost‐effectiveness</scp>
Authors: Shayan Barootchi, Lorenzo Tavelli, Jad Majzoub, Martina Stefanini, Hom‐Lay Wang, Gustavo Avila‐Ortiz
Journal: Periodontology 2000 (2022)

Abstract Alveolar ridge preservation is routinely indicated in clinical practice with the purpose of attenuating postextraction ridge atrophy. Over the past two decades numerous clinical studies and reviews on this topic have populated the literature. In recent years the focus has primarily been on analyzing efficacy outcomes pertaining to postextraction dimensional changes, whereas other relevant facets of alveolar ridge preservation therapy have remained unexplored. With this premise, we carried out a comprehensive evidence‐based assessment of the complications associated with different modalities of alveolar ridge preservation and modeled the cost‐effectiveness of different therapeutic modalities as a function of changes in ridge width and height. We conclude that, among allogeneic and xenogeneic bone graft materials, increased expenditure does not translate into increased effectiveness of alveolar ridge preservation therapy. On the other hand, a significant association between expenditure on a barrier membrane and reduced horizontal and vertical ridge resorption was observed, though only to a certain degree, beyond which the return on investment was significantly diminished.
HOXA9 forms a repressive complex with nuclear matrix–associated protein SAFB to maintain acute myeloid leukemia
Authors: Shuchi Agrawal-Singh, Jaana Bagri, George Giotopoulos, Dhoyazan M. A. Azazi, Sarah J. Horton, Cecile K. Lopez, Shubha Anand, Anne-Sophie Bach, Frances Stedham, Robin Antrobus, Jack W. Houghton, George S. Vassiliou, Daniel Sasca, Haiyang Yun, Anthony D. Whetton, Brian J. P. Huntly
Journal: Blood (2022)
Methodological Issues in Study of Daily Insulin Dose and Cancer Risk Among Patients With Type 1 Diabetes
Authors: Yin Zhang, Edward L. Giovannucci
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Translational nanomedicine potentiates immunotherapy in sarcoma by normalizing the microenvironment
Authors: Fotios Mpekris, Myrofora Panagi, Christina Michael, Chrysovalantis Voutouri, Masami Tsuchiya, Chihiro Wagatsuma, Hiroaki Kinoh, Atsushi Osada, Shiro Akinaga, Sei Yoshida, John D. Martin, Triantafyllos Stylianopoulos
Journal: Journal of Controlled Release (2022)
The industry impact of the American Medical Association’s Digital Medicine Payment Advisory Group (DMPAG)
Authors: Joseph C. Kvedar, Mirja Mittermaier, Jordan Pritzker
Journal: npj Digital Medicine (2022)

Abstract Digital medicine interventions are currently transforming health care and have created new efficiencies in the delivery process. The business model along with physician payment models are crucial drivers for the adoption of innovations. In the U.S., physician payment is mostly codified in the Current Procedural Terminology (CPT). Until recently, CPT codes related to digital medicine activities were mainly limited to telephone services. To embrace the evolving implementation of the various modalities of digital medicine, the American Medical Association (AMA) determined that a more comprehensive codeset is needed. Thus, the Digital Medicine Payment Advisory Group (DMPAG) was initiated in late 2016. Since then, the DMPAG has achieved a significant and measurable impact on digital medicine intervention adoption by introducing CPT codes for remote physiologic monitoring, remote therapeutic monitoring, artificial intelligence, and other digital innovations.
Testing for <i>EGFR</i> Variants in Pleural and Pericardial Effusion Cell-Free DNA in Patients With Non–Small Cell Lung Cancer
Authors: Kirsty W. C. Lee, Molly S. C. Li, Wanxia Gai, Yat Ming Lau, Allen K. C. Chan, Oscar S. H. Chan, Chee Khoon Lee, Rebecca M. W. Yeung, Sherwood Y. H. Fung, Wai F. Cheung, Vivian W. Chan, Linda Leung, Kenny N. P. Kam, Tony S. K. Mok
Journal: JAMA Oncology (2022)

Molecular testing in non-small cell lung cancer (NSCLC) is commonly limited by inadequate tumor sample. Plasma cell-free DNA (cfDNA) genotyping as a complementary test is specific but only moderately sensitive. Genotyping of cfDNA in pleural and pericardial effusion (PE-cfDNA) can further optimize molecular diagnostic yield and reduce the need for repeated biopsies.To prospectively validate droplet digital polymerase chain reaction (ddPCR) for detection of sensitizing EGFR variants and acquired Thr790Met variant (T790M) from PE-cfDNA in patients with NSCLC.This prospective diagnostic validation study was conducted between September 6, 2016, and January 21, 2021 at 2 major Hong Kong cancer centers. Patients with advanced NSCLC with both wild-type and variant EGFR status and exudative PE who underwent thoracocentesis or pericardiocentesis were randomly enrolled. Patients were either EGFR-tyrosine kinase inhibitor (TKI) naive (cohort 1) or EGFR-TKI treated but osimertinib naive (cohort 2). Enrolled patients underwent pleural- or pericardial-fluid and blood sampling for ddPCR EGFR testing. EGFR status results with ddPCR testing of PE-cfDNA and blood were compared with EGFR status in matched tumor biopsy or PE cell block samples.Specificity, sensitivity, and concordance of PE-cfDNA for detection of sensitizing EGFR variants and acquired T790M variation.Among 171 patients (54% female) enrolled, there were 104 in cohort 1 and 67 in cohort 2. In cohort 1, 37% (38/102) were EGFR-variant positive; PE-cfDNA showed 97% sensitivity (95% CI, 92%-100%), 97% specificity (95% CI, 93%-100%), and 97% concordance (ĸ = 0.94, P < .001) for the detection of sensitizing EGFR variants. It was more sensitive than plasma in detecting sensitizing EGFR variants (97% vs 74%, P < .001). In cohort 2, 38% (15 of 40) were positive for the EGFR T790M variant; PE-cfDNA showed 87% sensitivity (95% CI, 69%-100%), 60% specificity (95% CI, 41%-79%), and 70% concordance (ĸ = 0.42, P = .004) for acquired T790M. The EGFR T790M variant was detected in 51% of PE-cfDNA vs 25% of PE cell block samples.In this diagnostic study, EGFR variants could be accurately detected from PE-cfDNA in patients with NSCLC. More EGFR T790M was detected in PE-cfDNA than in guideline-recommended PE cell block preparations. These results suggest that PE-cfDNA can complement plasma and tumor genotyping for detecting EGFR variants in patients with advanced NSCLC.
VV116 versus Nirmatrelvir–Ritonavir for Oral Treatment of Covid-19
Authors: Zhujun Cao, Weiyi Gao, Hong Bao, Haiyan Feng, Shuya Mei, Peizhan Chen, Yueqiu Gao, Zhilei Cui, Qin Zhang, Xianmin Meng, Honglian Gui, Weijing Wang, Yimei Jiang, Zijia Song, Yiqing Shi, Jing Sun, Yifei Zhang, Qing Xie, Yiping Xu, Guang Ning, Yuan Gao, Ren Zhao
Journal: New England Journal of Medicine (2022)

Nirmatrelvir-ritonavir has been authorized for emergency use by many countries for the treatment of coronavirus disease 2019 (Covid-19). However, the supply falls short of the global demand, which creates a need for more options. VV116 is an oral antiviral agent with potent activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).We conducted a phase 3, noninferiority, observer-blinded, randomized trial during the outbreak caused by the B.1.1.529 (omicron) variant of SARS-CoV-2. Symptomatic adults with mild-to-moderate Covid-19 with a high risk of progression were assigned to receive a 5-day course of either VV116 or nirmatrelvir-ritonavir. The primary end point was the time to sustained clinical recovery through day 28. Sustained clinical recovery was defined as the alleviation of all Covid-19-related target symptoms to a total score of 0 or 1 for the sum of each symptom (on a scale from 0 to 3, with higher scores indicating greater severity; total scores on the 11-item scale range from 0 to 33) for 2 consecutive days. A lower boundary of the two-sided 95% confidence interval for the hazard ratio of more than 0.8 was considered to indicate noninferiority (with a hazard ratio of >1 indicating a shorter time to sustained clinical recovery with VV116 than with nirmatrelvir-ritonavir).A total of 822 participants underwent randomization, and 771 received VV116 (384 participants) or nirmatrelvir-ritonavir (387 participants). The noninferiority of VV116 to nirmatrelvir-ritonavir with respect to the time to sustained clinical recovery was established in the primary analysis (hazard ratio, 1.17; 95% confidence interval [CI], 1.01 to 1.35) and was maintained in the final analysis (median, 4 days with VV116 and 5 days with nirmatrelvir-ritonavir; hazard ratio, 1.17; 95% CI, 1.02 to 1.36). In the final analysis, the time to sustained symptom resolution (score of 0 for each of the 11 Covid-19-related target symptoms for 2 consecutive days) and to a first negative SARS-CoV-2 test did not differ substantially between the two groups. No participants in either group had died or had had progression to severe Covid-19 by day 28. The incidence of adverse events was lower in the VV116 group than in the nirmatrelvir-ritonavir group (67.4% vs. 77.3%).Among adults with mild-to-moderate Covid-19 who were at risk for progression, VV116 was noninferior to nirmatrelvir-ritonavir with respect to the time to sustained clinical recovery, with fewer safety concerns. (Funded by Vigonvita Life Sciences and others; ClinicalTrials.gov number, NCT05341609; Chinese Clinical Trial Registry number, ChiCTR2200057856.).
Association of COVID-19 Vaccination With Breakthrough Infections and Complications in Patients With Cancer
Authors: Inna Y. Gong, Abi Vijenthira, Melanie Powis, Andrew Calzavara, Aditi Patrikar, Rinku Sutradhar, Lisa K. Hicks, Drew Wilton, Simron Singh, Monika K. Krzyzanowska, Matthew C. Cheung
Journal: JAMA Oncology (2022)

Patients with cancer are known to have increased risk of COVID-19 complications, including death.To determine the association of COVID-19 vaccination with breakthrough infections and complications in patients with cancer compared to noncancer controls.Retrospective population-based cohort study using linked administrative databases in Ontario, Canada, in residents 18 years and older who received COVID-19 vaccination. Three matched groups were identified (based on age, sex, type of vaccine, date of vaccine): 1:4 match for patients with hematologic and solid cancer to noncancer controls (hematologic and solid cancers separately analyzed), 1:1 match between patients with hematologic and patients with solid cancer.Cancer diagnosis.Outcomes occurring 14 days after receipt of second COVID-19 vaccination dose: primary outcome was SARS-CoV-2 breakthrough infection; secondary outcomes were emergency department visit, hospitalization, and death within 4 weeks of SARS-CoV-2 infection (end of follow-up March 31, 2022). Multivariable cumulative incidence function models were used to obtain adjusted hazard ratio (aHR) and 95% CIs.A total of 289 400 vaccinated patients with cancer (39 880 hematologic; 249 520 solid) with 1 157 600 matched noncancer controls were identified; the cohort was 65.4% female, and mean (SD) age was 66 (14.0) years. SARS-CoV-2 breakthrough infection was higher in patients with hematologic cancer (aHR, 1.33; 95% CI, 1.20-1.46; P < .001) but not in patients with solid cancer (aHR, 1.00; 95% CI, 0.96-1.05; P = .87). COVID-19 severe outcomes (composite of hospitalization and death) were significantly higher in patients with cancer compared to patients without cancer (aHR, 1.52; 95% CI, 1.42-1.63; P < .001). Risk of severe outcomes was higher among patients with hematologic cancer (aHR, 2.51; 95% CI, 2.21-2.85; P < .001) than patients with solid cancer (aHR, 1.43; 95% CI, 1.24-1.64; P < .001). Patients receiving active treatment had a further heightened risk for COVID-19 severe outcomes, particularly those who received anti-CD20 therapy. Third vaccination dose was associated with lower infection and COVID-19 complications, except for patients receiving anti-CD20 therapy.In this large population-based cohort study, patients with cancer had greater risk of SARS-CoV-2 infection and worse outcomes than patients without cancer, and the risk was highest for patients with hematologic cancer and any patients with cancer receiving active treatment. Triple vaccination was associated with lower risk of poor outcomes.
Drug Sensitivity of Currently Circulating Mpox Viruses
Authors: Denisa Bojkova, Marco Bechtel, Tamara Rothenburger, Katja Steinhorst, Nadja Zöller, Stefan Kippenberger, Julia Schneider, Victor M Corman, Hannah Uri, Mark N Wass, Gaby Knecht, Pavel Khaykin, Timo Wolf, Sandra Ciesek, Holger F Rabenau, Martin Michaelis, Jindrich Cinatl
Journal: New England Journal of Medicine (2022)

suggest an increased incidence of ectopic pregnancy detected after abortion with the use of no-touch protocols. 5However, clinicians must maintain a high index of suspicion for ectopic pregnancy in persons presenting with suggestive symptoms, in particular in persons without confirmation of an intrauterine pregnancy before abortion.
Methodological Issues in Study of Daily Insulin Dose and Cancer Risk Among Patients With Type 1 Diabetes
Authors: Haydee Verduzco-Aguirre, Maria Eugenia Penados-Ovalle, Leonardo Guadalupe Mancillas-Adame
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Use of Single-Arm Trials for US Food and Drug Administration Drug Approval in Oncology, 2002-2021
Authors: Sundeep Agrawal, Shaily Arora, Laleh Amiri-Kordestani, R. Angelo de Claro, Lola Fashoyin-Aje, Nicole Gormley, Tamy Kim, Steven Lemery, Gautam U. Mehta, Emma C. Scott, Harpreet Singh, Shenghui Tang, Marc R. Theoret, Richard Pazdur, Paul G. Kluetz, Julia A. Beaver
Journal: JAMA Oncology (2022)

Single-arm trials have allowed for transformative therapies to be made available to patients expeditiously. However, using single-arm trials to support drug approval presents several challenges that must be carefully considered.Between January 1, 2002, and December 31, 2021, the US Food and Drug Administration granted 176 new malignant hematology and oncology indications based on single-arm trials, including 116 accelerated approvals (AAs) and 60 traditional approvals. Overall, 87 approvals (49%) were for new molecular entities or original biologics and 89 (51%) were supplemental indications. Response rate (RR) was the most common end point used to support approval in these single-arm trials (173 of 176 [98%]). Of the 116 AAs based on single-arm trials, 45 (38%) fulfilled their postmarketing requirement to verify clinical benefit, 61 (52%) are pending verification of benefit, and 10 (9%) were withdrawn from the market as of December 31, 2021. Most (56 of 61 [92%]) AAs based on single-arm trials pending verification of benefit occurred during the previous 5 years and have ongoing confirmatory trials as of December 2021.Single-arm trials have been a common development strategy to support regulatory approval as early-stage expansion cohorts with promising durable RRs have become more prevalent. In the appropriate context, single-arm trials using durable RRs can allow patients expedited access to novel therapies and will continue to serve a role in advancing drug development in oncology. However, single-arm trials have a smaller noncomparative safety data set, inability to use time-to-event end points, and other limitations that require careful consideration within the context of the disease and available therapies. The randomized clinical trial remains the preferred approach in clinical investigation.